In the immune system, TAM receptors
are used by cells such as macrophages and
dendritic cells to clean up dead cells. They
are also central inhibitors of the body's innate
immune response to bacteria, viruses and
other pathogens.

As reported in Cell Host and Microbe,
researchers in the labs of John A.T. Young and
Greg Lemke have discovered that a substance
called phosphatidylserine (PtdSer), found on
the surface of enveloped viruses (viruses with
an outer wrapping of a lipid membrane), binds
to extracellular proteins and activates TAM
receptors on immune cells. In dendritic cells,
a type of immune cell that interacts with T and
B cells to initiate the adaptive immune response,
TAM receptor activation turns off a set of genes
called interferons that play a key role in antiviral
defense. The findings suggest a unique way in
which TAM receptors contribute to the establishment
of viral infection by disabling the interferon
response. As a consequence, the interferon-stimulated
defense genes are not turned on, rendering
the target cell more vulnerable.

This is a previously unknown mechanism
for enveloped viruses, which are very common,
to inhibit the body's normal antiviral response.
Since PtdSer exposure seems to be a general
feature of enveloped viruses, the researchers say
many different viruses may use the mechanism
to counteract the antiviral response in cells with
TAM receptors.

Understanding this mechanism will allow researchers
to work on developing broad-spectrum
antiviral drugs that prevent viruses from shutting
down the interferon response in cells by blocking
TAM receptor activation. Young and Lemke
tested a small-molecule drug initially developed
for anti-cancer therapy that does just that, and
with other scientists around the country, they
are now testing other small-molecule drugs
that work, in large part, by blocking the virus's
ability to activate TAM receptors, leaving the
interferon-mediated antiviral response intact in
such viruses as West Nile, dengue, influenza,
Ebola, Marburg and hepatitis B. This is a
completely novel approach, says Young, and
if it works, it may prove effective at clearing
enveloped viruses during the acute phase of
infection and perhaps in chronic viral infections
as well.